高通量数据分析急性髓系白血病关键节点基因及预后关联分析

Identification of Hubs genes and its correlation with the prognosis of acute myeloid leukemia based on high throughput data analysis

目的急性髓系白血病(acute myeloid leukemia,AML)是世界上常见的白血病之一,但其分子机制尚不清楚.本研究旨在利用多个AML数据集获得差异表达基因(differentially expressed gene,DEG)鉴定AML发生和进展中的关键基因.方法从基因表达综合数据库(Gene Expression Omnibus,GEO)下载AML微阵列数据集(GSE24395、GSE30029、GSE38865和GSE90062).鉴定DEGs并进行功能富集,构建蛋白质-蛋白质相,使用Cytoscape进行模块分析获得关键基因(Hubs),并结合癌症和肿瘤基因图谱(Cancer Genome Atlas,TCGA)临床数据进行生存及表达分析.结果共鉴定出134个DEG (fold chang>1,P<0.01),基因富集分析涉及RNA聚合酶Ⅱ启动子转录的正调控(c=17.967,P=0.011)、中性粒细胞脱颗粒(c=18.625,P=0.017)、整合素介导的细胞黏附调节(c=17.862,P=0.017)、中性粒细胞介导的免疫(c=17.624,P=0.017)和癌症中的转录失调(c=14.786,P=00.031)等.鉴定了16个Hub基因,TCGA临床数据表达分析提示,CYBB(t=0.368,P=0.012)和CYFIP2(t=2.097,P=0.038)在AML的不同生存状态中异常表达.生存分析显示,SERPINE1(P=0.031)和ITGAM(P=0.049)可能参与了AML侵袭或复发.结论 DEG和Hub分析筛选基因有助于理解AML发生和进展的分子机制,为AML的治疗及预后判断提供候选靶点.

OBJECTIVE Acute myeloid leukemia( AML) is one of the most common leukemias in the world,but its molecular mechanism is still not well understood. The aim of this study was to obtain genes with differential expression by multiple AML datasets and identify key genes in the development and progression of AML. METHODS The AML microarray dataset (GSE24395, GSE30029, GSE38865, GSE90062) was downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes(DEGs) were identified and functionally enriched,a protein-protein interaction network (PPI) was constructed. Cytoscape was used for module analysis to obtain fundamental genes ( Hubs genes) and combined with TCGA clinical data for survival and expression analysis. RESULTS A total of 134 DEGs were identified (fold chang>l,P<0. 01). Gene enrichment analysis included positive regulation of RNA polymerase Ⅱ promoter transcriptions (c= 17. 967, P = 0. 011), neutrophil degranulation (c = 18.625, P = 0. 017), integrin-mediated cells (c = 17. 862,P = 0. 017),adhesion regulation,neutrophil-mediated immunity (c= 17. 624,P = 0. 017),transcriptional disorders in cancer (c=14. 786,P = 00. 031). Sixteen Hub genes were identified. Based on TCGA clinical data expression analysis, CYBB (t=0. 368,P=0. 012) and CYFIP2 (t=2. 097,P = 0. 038) were abnormally expressed in different living conditions of AML. Survival analysis showed that SERPINE1 (P = 0. 031) ITGAM (P = 0. 049) may be involved in invasion or recurrence of AML. CONCLUSION The analysis of DEGs and Hub analysis of genes can contribute to understand the molecular mechanism of AML occurrence and progression,provide a candidate for the treatment and prognosis of AML.